Ganglioside-induced differentiation-associated protein 1 (GDAP1)

Ganglioside-induced differentiation-associated protein 1 (GDAP1) is a mitochondrial outer membrane protein structurally related to the glutathione S-transferase (GST) family, but lacking GST enzymatic activity[1][3][5]. It plays a critical role in regulating mitochondrial fission and networking without inducing apoptosis, and is involved in maintaining mitochondrial morphology as well as interactions with the cytoskeleton, particularly through β-tubulin binding[1][5]. GDAP1 is essential for proper neuronal function, especially in peripheral nerves: mutations lead to both axonal and demyelinating forms of Charcot-Marie-Tooth (CMT) neuropathy, with resulting motor and sensory dysfunction, abnormal mitochondrial structure, calcium homeostasis defects, and neuronal degeneration[2][4][6]. GDAP1 has a unique dimeric structure, associates with the mitochondrial outer membrane via a transmembrane domain, and is believed to modulate mitochondrial-cytoskeletal interactions and possibly lipid metabolism at the membrane interface[1][3][5]. There are currently no known drugs that specifically target GDAP1, and its most clinically relevant role is as a diagnostic marker for certain forms of inherited neuropathies[2][4].

Other names

CMT4ACMT2KCharcot-Marie-Tooth neuropathy 4AGDAP1ganglioside induced differentiation associated protein 1

Null (no approved drugs directly targeting GDAP1; therapeutic approaches focus on genetic or supportive treatments)[2]